There is considerable evidence suggesting that genetic factors predispose to the development of obesity. Recent work from several laboratories has begun to elucidate the molecular basis of several forms of genetic obesity in rodents. We have initiated a project to extend the work emanating from the positional cloning of the murine obese gene. The gene encodes a peptide hormone (i.e., leptin) that is secreted by adipose tissue. We have used this knowledge to develop expression vectors for synthesis of recombinant murine and human leptin. Using recombinant leptin, we have initiated efforts to search for a cell surface receptor that mediates the action of leptin upon target cells. In addition, we have obtained antibodies to leptin, and are attempting to establish a radioimmunoassay to measure leptin levels in plasma.